Glutamate transporter-mediated glutamate secretion in the mammalian pineal gland.
Glutamate transporters are expressed throughout the CNS where their major role is to clear released glutamate from presynaptic terminals. Here, we report a novel function of the transporter in rat pinealocytes. This electrogenic transporter conducted inward current in response to L-glutamate and L- or D-aspartate and depolarized the membrane in patch-clamp experiments. Ca2+ imaging demonstrated that the transporter-mediated depolarization induced a significant Ca2+ influx through voltage-gated Ca2+ channels. The Ca2+ rise finally evoked glutamate exocytosis as detected by carbon-fiber amperometry and by HPLC. In pineal slices with densely packed pinealocytes, glutamate released from the cells effectively activated glutamate transporters in neighboring cells. The Ca2+ signal generated by KCl depolarization or acetylcholine propagated through several cell layers by virtue of the regenerative "glutamate-induced glutamate release." Therefore, we suggest that glutamate transporters mediate synchronized elevation of L-glutamate and thereby efficiently downregulate melatonin secretion via previously identified inhibitory metabotropic glutamate receptors in the pineal gland.
Kim
Mean-Hwan
MH
Department of Physics, Pohang University of Science and Technology, Kyungbuk 790-784, Republic of Korea.
Uehara
Shunsuke
S
Muroyama
Akiko
A
Hille
Bertil
B
Moriyama
Yoshinori
Y
Koh
Duk-Su
DS
D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D018942:Macrolides / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010870:Pineal Gland / Q000166:cytology / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D027322:Amino Acid Transport System X-AG; D002712:Chlorides; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018942:Macrolides; C120673:benzyloxyaspartate; D002586:Cesium; D001224:Aspartic Acid; D018698:Glutamic Acid; C020889:dihydrokainic acid; D011189:Potassium Chloride; C040929:bafilomycin A1; C028019:cesium chloride; D008274:Magnesium; D008550:Melatonin; D007608:Kainic Acid; D002118:Calcium